The mechanism of the angiogenic response has been further studied by extending the search for chemically defined compounds able to mobilize capillary endothelium. The chemotactic activity on endothelium of extract from PGE1 treated corneas was found to bind to a gelatin-sepharose affinity column. On the assumption that fibronectin could be involved in the chemotactic event we established that (a) mobilization of endothelium by a chemoattractant is most efficient when fibronectin forms the substratum on which the endothelium adheres (b) monoclonal antifibronectin serum blocks the mobilization of capillary endothelium on fibronectin substrate (c) Fibronectin alone or heparin alone do not mobilize capillary endothelium but in combination they substantially enhance mobilization (d) The whole molecule of both fibronectin or heparin is not necessary for the mobilization, fragments of both molecules are sufficient. The characteristics of these fragments are being investigated. The work of the past year has produced evidence to sustain the hypothesis that molecules normally present in the extracellular compartment may act as angiogenesis factors when fragmented by lytic enzymes.